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Characterization of MGMT and EGFR protein expression in glioblastoma and association with survival

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Abstract

Purpose

Understanding the molecular landscape of glioblastoma (GBM) is increasingly important in the age of targeted therapy. O-6-Methylguanine-DNA methyltransferase (MGMT) promoter methylation and EGFR amplification are markers that may play a role in prognostication, treatment, and/or clinical trial eligibility. Quantification of MGMT and EGFR protein expression may offer an alternative strategy towards understanding GBM. Here, we quantify baseline expression of MGMT and EGFR protein in newly diagnosed GBM samples using mass spectrometry. We correlate findings with MGMT methylation and EGFR amplification statuses and survival.

Methods

We retrospectively identified adult patients with newly diagnosed resected GBM. MGMT and EGFR protein expression were quantified using a selected reaction monitoring mass spectrometry assay. Protein levels were correlated with MGMT methylation and EGFR amplification and survival data.

Results

We found a statistically significant association between MGMT protein expression and promoter methylation status (p = 0.02) as well as between EGFR protein expression and EGFR amplification (p < 0.0001). EGFR protein expression and amplification were more tightly associated than MGMT protein expression and methylation. Only MGMT promoter methylation was statistically significantly associated with progression-free and overall survival.

Conclusions

Unlike EGFR protein expression and EGFR amplification which are strongly associated, only a weak association was seen between MGMT protein expression and promoter methylation. Quantification of MGMT protein expression was inferior to MGMT methylation for prognostication in GBM. Discordance was observed between EGFR amplification and EGFR protein expression; additional study is warranted to determine whether EGFR protein expression is a better biomarker than EGFR amplification for clinical decisions and trial enrollment.

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Acknowledgements

The authors acknowledge the support of the NIH Cancer Center Support Grant P30 CA008748. The authors wish to thank Susan Atlas and Moira McGrath for their editorial assistance.

Funding

This study was funded in part by NantOmics which holds the patent for the SRM assay discussed in the manuscript. The authors acknowledge the support of the NIH Cancer Center Support Grant P30 CA008748.

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Authors and Affiliations

  1. Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA

    Lauren R. Schaff & Andrew L. Lin

  2. NantOmics, Culver City, CA, 90230, USA

    Dongyao Yan, Sheeno Thyparambil, Yuan Tian, Fabiola Cecchi & Todd Hembrough

  3. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA

    Marc Rosenblum

  4. Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA

    Anne S. Reiner & Katherine S. Panageas

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  1. Lauren R. Schaff
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  4. Yuan Tian
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Correspondence to Lauren R. Schaff.

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Conflict of interest

Authors Schaff, Rosenblum, Reiner, Panageas, and Lin have no conflict of interest. Authors Thyparambil and Hembrough have a patent for the SRM assay discussed in this manuscript and are employees of NantOmics. Authors Yan, Tian, and Cecchi are employees of NantOmics.

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This article does not contain any studies with human participants or animals performed by any of the authors. This study was approved by the Internal Review Board at MSKCC.

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Schaff, L.R., Yan, D., Thyparambil, S. et al. Characterization of MGMT and EGFR protein expression in glioblastoma and association with survival. J Neurooncol 146, 163–170 (2020). https://doi.org/10.1007/s11060-019-03358-x

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